It represents a closely integrated series of studies on cognitive, neuroimaging, genetic and pathologic measures concerning the boundary between aging and Alzheimer's disease (AD). The overarching goal of our research continues to be to characterize the prodromal phase of Alzheimer's disease (AD) and to differentiate it from changes related to normal aging, in order to predict who will develop AD many years before individuals develop a diagnosable dementia. The subjects we will evaluate consist of three groups of individuals; those we are currently following (known as Cohort 1 and 2) and a third cohort (Cohort 3 that we propose to recruit to provide sufficient sample size for longitudinal analyses with the subjects). Four interrelated areas are included: Neuropsychological assessment (Project by Albert), Single Photon Emission Computed Tomography (SPECT) (Project by Johnson), structural magnetic resonance imaging (MRI) (Project by Killiany) and functional magnetic resonance imaging (fMRI) (Project by Sperling). Four Cores will provide essential support to the projects: the Administrative and Clinical Core will be responsible for subject recruitment, evaluation, and follow-up, the Data Management and Statistical Core will maintain a central Database, provide statistical consultation and complete integrative and complex statistical analyses; the Genetics Core will provide genotyping and the Neuropathology Core will provide quantitative neuropathological data on subjects who come to autopsy and will evaluate plasma A-beta annually on the subjects.